N,N,N',N'-Tetramethylethylenediamine → Dimethyl 2-(1,3-dioxoisoindolin-2-yl)-2-fluoropentane-1,5-dioate

HRID 363439Notes

Reaction equation

HRID 363439 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[C:13]([O:15][CH3:16])=[O:14].CN(C)CCN(C)C.C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:46])(=O)=O)=CC=1>O1CCCC1>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[C:12]([F:46])([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[C:13]([O:15][CH3:16])=[O:14]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 272791Dimethyl 2-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)pentanedioateHCID 588007N-FluorobenzenesulfonimideHCID 178418339Butyllithium

Product 1

HCID 21847931Dimethyl 2-(1,3-dioxoisoindolin-2-yl)-2-fluoropentane-1,5-dioate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of dimethyl 2-(1,3-dioxoisoindolin-2-yl)-pentane-1,5-dioate (1.0 g, 3.3 mmol) and tetramethylethylene diamine (0.5 g, 4.3 mmol) in tetrahydrofuran (10 mL) is added 2.5M n-butyl lithium (1.6 mL, 4 mmol,) at -79° C. After 30 minutes, N-fluorobenzenesulfonimide (1 g, 3.2 mmol) is added to the mixture which then is allowed to reach room temperature. The solvent is removed in vacuo and the residue is stirred with methylene chloride (100 mL) for 10 minutes. The organic layer is washed with water and brine (30 mL each), and dried over sodium sulfate. The solvent is removed in vacuo to yield dimethyl 2-(1,3-dioxoisoindolin-2-yl)-2-fluoropentane-1,5-dioate which is further purified by chromatography and converted to 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline as described above in Part D of Example 9.

Workup

  1. customto reach room temperature
  2. customThe solvent is removed in vacuo
  3. washThe organic layer is washed with water and brine (30 mL each)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-01ad4f1cc6ac46bab9b8f0b62d33118f
Source dataset
uspto-grants-1999_02
Patent number
US05874448

Reaction notes

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